The main purpose of the project is to investigate the molecular mechanisms of muscarinic cholinergic action; to study the presynaptic regulation of acetylcholine release, the postsynaptic activation of muscarinic receptors and the role of guanosine -3'5'-cyclic monophosphate in synaptic function. In preparations from rat hippocampus the role of muscarinic autoreceptors in the acetylcholine release and the different possible mechanisms of autoinhibition are studied. Agonist and antagonist binding to the postsynaptic muscarinic receptor is studied. The effects of acute and chronic treatment with psychoactive drugs on muscarinic receptor mediated mechanisms is under study. The different mechanisms for induction of muscarinic supersensitivity in the hippocampus by septal lesion and chronic atropine treatment are under study. Antagonist and agonist binding studies on material from human brain of control and Alzheimer dementia patients are in progress. Muscarinic and H1-histaminergic receptor mediated increases in cGMP levels in neuroblastoma (NIE 115) cells are under study.